De Summa Simona, Lasorella Antonia, Strippoli Sabino, Giudice Giuseppe, Guida Gabriella, Elia Rossella, Nacchiero Eleonora, Azzariti Amalia, Silvestris Nicola, Guida Michele, Guida Stefania, Tommasi Stefania, Pinto Rosamaria
Pharmacogenetics and Molecular Diagnostic Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Front Mol Biosci. 2021 Mar 5;7:555630. doi: 10.3389/fmolb.2020.555630. eCollection 2020.
Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs ( = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.
黑色素瘤具有复杂的分子背景，多个基因参与其发生和发展。新一代测序平台的出现使得能够同时评估多个基因，从而为黑色素瘤的遗传学研究带来了新的见解。我们使用靶向新一代测序panel研究了一组能够区分多原发性黑色素瘤（MPM）与单部位原发性黑色素瘤（SPM）发生的种系突变。我们的研究共纳入了39例患者，其中20例为SPM，19例为MPM。使用定制的靶向测序panel进行新一代分析，该panel包含32个已知在多种致癌途径中起作用的基因，例如参与DNA修复、色素沉着、激酶调节、细胞周期控制和衰老的基因。我们发现，与SPM相比，PIK3CA:p.I391M与MPM之间存在显著相关性， = 0.031；与MPM相比，CYP1B1:p.N453S与SPM之间存在关联趋势（ = 0.096）。我们还发现，两个亚组在8个基因（CYP1B1:p.N453S、BAP1:p.C39fs、PIK3CA:p.I391M、CDKAL1:c.1226_1227TG、POLE:p.V1161fs、OCA2:p.R419Q、OCA2:p.R305W、MC1R:p.V60L、MGMT:p.L115F）中共有9种改变，这表明这些基因可能在黑色素瘤的发生中起作用。总之，尽管患者队列较小，但我们发现种系突变，如PIK3CA和CYP1B1的突变，可能有助于SPM和MPM的差异发生。
